OBJECTIVES:  The Hatch-Waxman Act of 1984 facilitated the market entry of generic drugs while protecting innovator patent rights, encouraging continued biopharmaceutical investment in research and development (R&D). We evaluated the impact of generics on drug volume and expenditures in oncology. METHODS:  Trends in annual sales volume and expenditures of generic and brand-name therapeutic oncology prescription drugs were assessed from 2005-14 from the IMS MIDAS database of audited biopharmaceutical sales in the US. Volume was measured using standard units (SU), defined as the smallest dose of a product. Sub-analyses were conducted for breast (BC) and colorectal cancer (CRC). The cost-savings generated from generic entry from 2006-14 was estimated. RESULTS:  For overall oncology, generics represented 69.1-85.6% of total drug volume. Among brand products with generic entry (N = 21), average sales were $383 million (M) in the year prior to and $39M in the year after generic entry (-90%). Generic entry of oncology drugs over the period 2006-14 resulted in total cost-savings of $20.4 billion (B), with an average cost-savings of $970M. For BC and CRC, generic spending and volume increased from 2005-14. Generic entry resulted in total cost-savings of $10.9B in BC (N = 7) and $7.4B in CRC (N=3). For BC and CRC, average brand sales decreased by 95% and 86% from the year prior to the year after generic entry, respectively. CONCLUSIONS:  Generic utilization represents an increasing majority of total oncology volume. Significant cost savings were generated with the entry of steeply discounted generics. The lifecycle of a brand drug, from to patent loss, fuels the generic pipeline and supports the continued development of the next generation of innovative therapies, providing substantial value to patients, the healthcare system and society. Further savings may soon be realized with the generic entry of breakthrough products, such as imatinib and rituximab.